Fetal macrophages assist in the repair of ruptured amnion through the induction of epithelial-mesenchymal transition

The premature rupture of the amniotic sac, a condition referred to as a preterm prelabor rupture of membranes (pPROM), is a leading cause of preterm birth. In some cases, these ruptured membranes heal spontaneously. Here, we investigated repair mechanisms of the amnion, a layer of epithelial cells in the amniotic sac closest to the em-bryo. Macrophages migrated to and resided at rupture sites in both human and mouse amnion. A process called epithelial-mesenchymal transition (EMT), in which epithelial cells acquire a mesenchymal phenotype and which is implicated in tissue repair, was observed at rupture sites. In dams bearing macrophage-depleted fetuses, the re-pair of amnion ruptures was compromised, and EMT was rarely detected at rupture sites. The migration of cul-tured amnion epithelial cells in wound healing assays was mediated by EMT through transforming growth factor-0 (TGF-0)-Smad signaling. These findings suggest that fetal macrophages are crucial in amnion repair because of their ability to induce EMT in amnion epithelial cells.